Activation of gp130 signaling in vivo by the IL-6 super-agonist K-7/D-6 accelerates repopulation of lymphoid organs after irradiation

Daniela Frasca, Gino Doria, Paola Barattini, Francesco Guidi, AnnaLaura Salvati, Carlo Toniatti, Gennaro Ciliberto

Research output: Contribution to journalArticle

Abstract

Stimulation of the gp130 signaling pathway by IL-6 is known to contribute significantly to hematopoietic expansion in vitro, mostly in combination with other cytokines. In the present study we have investigated whether a similar effect can be observed also in vivo using short-term assays in which irradiated mice were analyzed for repopulation of lymphoid organs. Mice were injected with a combination of soluble IL-6Rα either with wild-type (wt) human IL-6 or with an IL-6 variant, called K-7/D-6, that shows a 70-fold higher IL-GRα affinity. We observed that while wt IL-6 was able to induce a partial effect only in combination with IL-3, K-7/D-6 bypassed the need for IL-3 and yielded complete recovery. In lethally irradiated mice reconstituted with syngeneic bone marrow cells K-7/D-6 strongly accelerated the repopulation of thymus and spleen and hastened blood neutrophil recovery. These results underscore the potential of the gp130 signaling pathway in hematopoietic reconstitution after myeloablative regimens and open the possibility to fully exploit it with a super-active IL-6 variant.

Original languageEnglish
Pages (from-to)300-310
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number1
DOIs
Publication statusPublished - 1999

Keywords

  • gp130
  • IL-6
  • Irradiation
  • Lymphoid organ

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Activation of gp130 signaling in vivo by the IL-6 super-agonist K-7/D-6 accelerates repopulation of lymphoid organs after irradiation'. Together they form a unique fingerprint.

  • Cite this